PDS Biotech is a clinical-stage immunotherapy company developing a growing pipeline of molecularly targeted cancer and infectious disease immunotherapies based on the Company’s proprietary Versamune® and Infectimune™ T-cell activating technology platforms. Our Versamune®-based products have demonstrated the potential to overcome the limitations of current immunotherapy by inducing in vivo, large quantities of high-quality, highly potent polyfunctional tumor specific CD4+ helper and CD8+ killer T-cells. PDS Biotech has developed multiple therapies, based on combinations of Versamune® and disease-specific antigens, designed to train the immune system to better recognize diseased cells and effectively attack and destroy them. The Company’s pipeline products address various cancers including HPV16-associated cancers (anal, cervical, head and neck, penile, vaginal, vulvar) and breast, colon, lung, prostate and ovarian cancers.
Robert LeBoyer, Senior Vice President, Equity Research Analyst, Biotechnology, Noble Capital Markets, Inc.
Refer to the full report for the price target, fundamental analysis, and rating.
PDS Biotech Updated Phase 2 Survival Data. PDS Biotech updated its Phase 2 VERSATILE-002 data presented at the ACSO conference in May 2023. This trial is testing the combination of PDS0101 and pembrolizumab (Keytruda, from Merck) in recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC). The data presented at ASCO in May included patients followed up to 12 months, while the update followed patients up to 24 months.
Survival Of 74% Is A Significant Improvement. Patients that were followed for two years had an overall survival rate of 74% compared with published studies showing less than 30% survival. Overall survival at 12 months at 80% compares with published results of 30% to 50%. Tumor shrinkage was seen in 60% (31/52) and confirmed by second MRI scan (overall response rate, ORR) in 27% (14/52 patients). Treatment related adverse events (TRAEs) were limited to Grade 3 in 13% (8/55) patients, and none had Grade 4 or Grade 5. We see these data as significantly improved over pembrolizumab alone or with chemotherapy.
Equity Research is available at no cost to Registered users of Channelchek. Not a Member? Click ‘Join’ to join the Channelchek Community. There is no cost to register, and we never collect credit card information.
This Company Sponsored Research is provided by Noble Capital Markets, Inc., a FINRA and S.E.C. registered broker-dealer (B/D).
*Analyst certification and important disclosures included in the full report. NOTE: investment decisions should not be based upon the content of this research summary. Proper due diligence is required before making any investment decision.
Pharmaceutical giant Eli Lilly is expanding its cancer treatment portfolio into a promising new area by acquiring POINT Biopharma, a company developing radioactive drugs that precisely target tumors, for $1.4 billion.
POINT specializes in radioligand therapies, an emerging approach to cancer treatment that uses radioactive particles linked to molecules that bind to receptors on cancer cells. This enables the radiation to selectively kill tumors while limiting damage to healthy tissue.
Lilly is paying $12.50 per share in cash for POINT, an 87% premium over the stock’s latest closing price. The deal will give Lilly control of POINT’s pipeline of radioligand therapy candidates, which includes two late-stage experimental drugs.
One drug, PNT20021, targets prostate cancer tumors by binding to a protein called PSMA. Study data expected later this year will show whether it extends the lives of men with metastatic castration-resistant prostate cancer.
The other late-stage drug, PNT20031, homes in on neuroendocrine tumor cells via their somatostatin receptors. It may provide a new option for patients with advanced gastroenteropancreatic neuroendocrine tumors.
Beyond these lead programs, POINT has several earlier stage radioligands in development for cancers of the breast, lung, and brain. Lilly gains full access to progress these toward human testing.
The deal also gives Lilly two specialized facilities Point has built to produce and research radioligands. Manufacturing the drugs involves linking medical radioisotopes like actinium-225 to the targeting molecules, which requires nuclear expertise.
Jacob Van Naarden, head of Lilly’s oncology division, touted the promise of radioligands to safely destroy cancer while avoiding the side effects of traditional chemo. “We are excited by the potential of this emerging modality,” he said.
Lilly has been growing its cancer treatment business in recent years through deals for other firms’ drug candidates and technologies. The POINT acquisition similarly expands Lilly’s footprint into an area well-suited for precision medicine.
The U.S. Food and Drug Administration has already approved over a half dozen radioligand therapies from Lilly competitors like Novartis. Their success is driving a surge of investment and deal-making in the radiopharmaceutical field.
But analyst Geoffrey Porges of SVB Securities thinks Lilly overpaid for POINT. “We believe the valuation fails to reflect the very high risks inherent in drug development,” he wrote in a note to investors.
Porges added that Lilly may need to invest over $2 billion more to fully develop POINT’s pipeline over the next 5-7 years, with no certainty the drugs will pan out.
Lilly expects the acquisition to close by the end of 2023 after gaining required antitrust and regulatory approvals. The majority of POINT shareholders also must tender their shares as part of the agreement.
The deal marks Lilly’s second major oncology purchase in 2022. It paid $1.1 billion earlier in the year access to cancer drug candidates from China’s Zymeworks. With POINT, Lilly is now positioned as a leader across multiple next-wave approaches in the high-stakes race to develop better cancer treatments.
Shares of MAIA Biotechnology were trading higher Tuesday after the company announced that the FDA has cleared its application to test its experimental cancer therapy THIO in patients in the United States.
MAIA Biotech is developing THIO as a novel immunotherapy approach for advanced non-small cell lung cancer (NSCLC). With FDA clearance of its Investigational New Drug (IND) application, the company can now include U.S. cancer patients in its ongoing mid-stage trial evaluating THIO’s safety and efficacy.
This regulatory win is driving investor enthusiasm and higher trading volume for MAIA stock today.
About MAIA Biotech and THIO
MAIA Biotech is a clinical-stage immunotherapy company aiming to improve cancer treatment by targeting telomeres. Telomeres play an important role in cancer cell survival and resistance to standard therapies.
The company’s lead therapy THIO represents a first-in-class telomere-targeting agent for NSCLC. Early preclinical research indicates THIO can induce cancer cell death and stimulate anti-tumor immune responses.
MAIA is positioning THIO as a second or third line of treatment for NSCLC patients who have stopped responding to initial immunotherapy. The company sees THIO’s novel approach as a way to improve outcomes in this hard-to-treat population.
Phase 2 Trial Details
THIO is currently being tested in a Phase 2 clinical trial involving sites across Europe, Asia Pacific, and now with FDA clearance, the United States.
The trial is evaluating THIO in combination with the PD-1 checkpoint inhibitor Libtayo in advanced NSCLC patients. Researchers want to see if giving THIO first to “prime” the immune system, followed by Libtayo, can enhance and prolong the immune response against cancer cells.
The primary goal is assessing THIO’s safety and antitumor activity based on overall response rates. Secondary goals include evaluating biomarkers and overall survival. The trial expects to enroll approximately 90 patients total.
Next Steps for MAIA
While still early stage, the FDA clearance represents an important milestone for MAIA as it works to expand THIO’s potential reach. Being able to include U.S. sites should support faster enrollment and generate data from a larger, more diverse patient population.
Positive Phase 2 results would support advancing to a pivotal Phase 3 study, which the company hopes could lead to regulatory approval. MAIA sees a multi-billion dollar market opportunity in later-line NSCLC treatment.
The company is also exploring THIO’s potential in other cancer types like melanoma, prostate cancer, and multiple myeloma.
Why Investors are Excited
FDA clearance of THIO’s IND removes a key regulatory hurdle for MAIA. Being able to test the therapy in the major U.S. market is critical for the smaller biotech company.
Today’s stock move reflects investors’ increased confidence in THIO’s outlook and MAIA’s ability to execute on development plans. If the Phase 2 trial goes well, it would further validate THIO’s novel approach and cancer-fighting potential.
While still highly speculative given the early stage, MAIA represents an intriguing immunotherapy play for investors interested in emerging approaches for hard-to-treat cancers. The company’s focus on telomere biology and unique combination strategy with Libtayo differentiate it from other biotechs.
MAIA stock could continue to be volatile in the months ahead as Phase 2 data approaches. But the FDA clearance has put a spotlight on this previously lesser known name. For investors open to some risk, MAIA may be a cancer immunotherapy stock to have on the radar.
Calidi Biotherapeutics has completed its merger with special purpose acquisition company First Light Acquisition Group (FLAG), debuting as a publicly traded cancer immunotherapy company. The combined entity, now named Calidi Biotherapeutics, Inc., will commence trading on the NYSE American under ticker symbols “CLDI” and “CLDI WS” on September 13.
The merger provides Calidi with gross proceeds of approximately $28 million before expenses and debt repayments. This consists of $25 million raised in a concurrent private offering, $1 million in cash from FLAG’s trust, and $2 million in PIPE and non-redemption agreements.
Founded in 2014, Calidi is developing first-in-class immunotherapies using allogeneic stem cells to deliver targeted cancer treatments. The SPAC deal enables the company to continue advancing its pipeline as a publicly listed firm.
Calidi’s lead candidates CLD-101 and CLD-201 leverage proprietary platforms called NeuroNova and SuperNova. Both utilize allogeneic stem cells loaded with oncolytic viruses that directly infect and kill tumor cells.
CLD-101, which employs neural stem cells, is currently in a Phase 1 trial for recurrent high-grade glioma brain tumors. Interim data is expected in 2024. CLD-201 uses mesenchymal stem cells to treat advanced solid tumors, with a Phase 1/2 study slated for 2024.
According to Calidi CEO Allan Camaisa, the IPO “will allow us to push the boundaries of cell-based virotherapies and continue to research novel ways to eradicate cancer.”
SPACs have become an increasingly popular alternative to traditional IPOs in the biotech sector. Also known as “blank check companies”, SPACs raise capital through an IPO and then merge with a private entity to take it public. This allows the operating company to avoid some of the uncertainty associated with a traditional public debut.
First Light Acquisition Group, led by CEO Tom Vecchiolla, raised $172.5 million in its own IPO in May 2021. The team then sought a merger target that could benefit from the injection of public capital. They ultimately settled on clinical-stage Calidi and its novel immunotherapy approach.
In addition to the SPAC proceeds, Calidi has secured a $10 million forward purchase agreement from several institutional investors. It also intends to execute a $50 million purchase agreement with Lincoln Park Capital Fund.
Between its strengthened balance sheet and non-dilutive financing options, Calidi believes it now has the runway to advance its programs into 2025 without need for further equity funding.
According to Vecchiolla, “We are excited to see Calidi continue to grow as they transition into a public company and look forward to their clinical pursuit of new treatment options for patients everywhere in need.”
The merger completes Calidi’s transformation into a publicly traded company. With shares soon to start trading on the NYSE American under ticker “CLDI”, the company is poised to continue developing its promising immunotherapy candidates for cancer patients in need of new treatment options.
Mainz Biomed (NASDAQ:MYNZ) announced highly positive results this week from its ColoFuture clinical trial evaluating the integration of novel mRNA biomarkers into its ColoAlert screening test for colorectal cancer. The results demonstrated ColoAlert’s strong performance for detecting colorectal cancer and advanced adenomas, while also identifying promising biomarkers to further improve early detection capabilities.
The ColoFuture study is a multi-center international trial assessing whether integrating recently acquired mRNA biomarkers from Université de Sherbrooke can enhance ColoAlert’s sensitivity and specificity profile. ColoAlert is Mainz’s flagship product, a simple yet highly accurate home-based test using stool samples to detect colorectal cancer and advanced precancerous adenomas.
The product is already commercialized across Europe and select international territories. However, ColoFuture aimed to identify ways to further extend ColoAlert’s technical capabilities in preparation for an upcoming U.S. clinical trial that could lead to FDA approval.
Interim analysis from the ColoFuture trial included 220 subjects across centers in Germany, Norway and Denmark. On the primary endpoints for colorectal cancer detection, ColoAlert achieved 94% sensitivity and 97% specificity after integrating the novel mRNA biomarkers.
For identifying advanced adenomas, a key precursor to cancer, the updated test demonstrated 81% sensitivity. According to Mainz Biomed CEO Guido Baechler, “The power to detect lesions in a pre-cancerous stage can change the entire CRC diagnostic landscape. If advanced adenomas are identified early, they are curable.”
The positive data catalyzed strong trading volume as Mainz Biomed’s stock price rose 15% on over 1.5 million shares traded. The market enthusiastically welcomed the results.
The mRNA biomarkers evaluated in ColoFuture were specifically selected from research at Université de Sherbrooke. Published analysis of the biomarkers showed ability to detect signals from patients with either colorectal cancer or advanced adenomas. Mainz Biomed acquired these biomarker rights in January 2022.
By treating patients before polyps progress to cancer, integrating these biomarkers into ColoAlert could help prevent colorectal cancer altogether. This could greatly improve patient outcomes and reduce the burden of this deadly disease.
The positive data provides validation of ColoAlert’s accuracy as a non-invasive screening tool. It also gives Mainz Biomed multiple novel mRNA biomarkers to integrate into its upcoming U.S. clinical trial, dubbed ReconAAsense, which could support FDA approval under the PMA pathway.
According to Baechler, “As we look forward to publishing and presenting the full dataset, we eagerly await the outcome from our ReconAAsense clinical trial which remains on track to report results in Q4 of this year.”
With colorectal cancer remaining a leading cause of cancer deaths, early detection is critical. ColoAlert offers a simple, at-home solution that people can easily incorporate into routine wellness screenings. The new biomarkers identified in ColoFuture could make the test accessible to even more patients.
Mainz Biomed continues to spearhead innovation in the field, leveraging the latest advances in genetics to improve detection. The impressive ColoFuture results provides further validation of ColoAlert’s accuracy, while also charting a path forward to commercialization in the U.S.
With pivotal FDA trial data on the horizon, Mainz Biomed is positioned to disrupt the market, offering an easy yet cutting-edge approach to potentially save lives through early colorectal cancer detection.
Biocept, Inc. (NASDAQ: BIOC) has signed a licensing agreement with Plus Therapeutics, Inc. (NASDAQ: PSTV) for Biocept’s proprietary CNSide cancer detection test. The non-exclusive deal further expands an existing partnership between the companies.
Under the agreement, Plus Therapeutics receives the right to use CNSide testing in clinical trials and commercially if approved by regulators. In return, Plus will pay Biocept $150,000 upfront in stock along with fees for each test performed.
CNSide detects, quantifies, and monitors tumor cells in cerebrospinal fluid to diagnose leptomeningeal metastases, a type of cancer affecting the brain and spinal cord membranes.
Take a look at PDS Biotechnology Corporation, a clinical-stage immunotherapy company developing a growing pipeline of targeted cancer and infectious disease immunotherapies.
Plus Therapeutics is currently using CNSide in a Phase 1/2a clinical trial of its targeted radiotherapy Rhenium 186 Obisbemeda for treating leptomeningeal metastases. The company will pay Biocept $6,000 for each test conducted at Biocept’s lab during the trial.
Once Biocept completes the technology transfer to enable Plus to run CNSide in-house, Plus will pay $300,000 plus $2,800 per test performed. Plus also has an option to negotiate for third-party exclusivity rights to CNSide for a $1 million payment.
The deal provides non-dilutive funding for Biocept as it seeks to establish CNSide as a standard of care. Biocept’s stock jumped 63% in pre-market trading on the news, while Plus Therapeutics rose 10%.
“We are gratified that Plus continues to recognize the value of CNSide in leptomeningeal metastases disease management,” said Biocept President and CEO Antonino Morales. “This agreement further validates the clinical utility of CNSide.”
Plus Therapeutics CEO Marc Hedrick stated CNSide is the “emerging gold standard” for diagnosing patients with leptomeningeal metastases. The licensing deal allows Plus to pair CNSide with its novel radiotherapeutic drug candidate.
The agreement highlights growing industry interest in leveraging Biocept’s proprietary technology to improve cancer detection and monitoring. As CNSide gains further validation, Biocept aims to secure additional partnerships and drive adoption of the test.
Take a moment to look at Onconova Therapeutics Inc., a clinical-stage biopharmaceutical company focused on discovering and developing novel products for cancer patients.
PDS Biotech is a clinical-stage immunotherapy company developing a growing pipeline of molecularly targeted cancer and infectious disease immunotherapies based on the Company’s proprietary Versamune® and Infectimune™ T-cell activating technology platforms. Our Versamune®-based products have demonstrated the potential to overcome the limitations of current immunotherapy by inducing in vivo, large quantities of high-quality, highly potent polyfunctional tumor specific CD4+ helper and CD8+ killer T-cells. PDS Biotech has developed multiple therapies, based on combinations of Versamune® and disease-specific antigens, designed to train the immune system to better recognize diseased cells and effectively attack and destroy them. The Company’s pipeline products address various cancers including HPV16-associated cancers (anal, cervical, head and neck, penile, vaginal, vulvar) and breast, colon, lung, prostate and ovarian cancers.
Robert LeBoyer, Senior Vice President, Equity Research Analyst, Biotechnology, Noble Capital Markets, Inc.
Refer to the full report for the price target, fundamental analysis, and rating.
PDS Reports 2Q23. PDS reported a 2Q23 loss of $11.5 million or $(0.37) per share and ended the quarter with $60.6 million in cash. Importantly, PDS completed the filing of its final clinical trial design required for the Phase 3 VERSATILE-003 trial testing PDS0101 in head and neck cancer, a milestone that should allow the start of the trial before YE2023.
The Phase 3 VERSATILE-003 Trial On Track To Start In 2023. PDS completed the FDA filing for the final protocols for the Phase 3 VERSATILE-003 trial, meeting the expected milestone. This filing includes the study design and manufacturing data (CMC section) that should allow the trial to begin before year-end. The trial will test the combination of PDS0101 with Keytruda (pembrolizumab, from Merck) against Keytruda alone in patients with HPV16+ head and neck cancer.
Equity Research is available at no cost to Registered users of Channelchek. Not a Member? Click ‘Join’ to join the Channelchek Community. There is no cost to register, and we never collect credit card information.
This Company Sponsored Research is provided by Noble Capital Markets, Inc., a FINRA and S.E.C. registered broker-dealer (B/D).
*Analyst certification and important disclosures included in the full report. NOTE: investment decisions should not be based upon the content of this research summary. Proper due diligence is required before making any investment decision.
Onconova Therapeutics is a clinical-stage biopharmaceutical company focused on discovering and developing novel products for patients with cancer. The Company has proprietary targeted anti-cancer agents designed to disrupt specific cellular pathways that are important for cancer cell proliferation. Onconova’s novel, proprietary multi-kinase inhibitor narazaciclib (formerly ON 123300) is being evaluated in a combination trial with estrogen blockade in advanced endometrial cancer. Based on preclinical and clinical studies of CDK 4/6 inhibitors, Onconova is also evaluating opportunities for combination studies with narazaciclib in additional indications. Onconova’s product candidate rigosertib is being studied in multiple investigator-sponsored studies. These studies include a dose-escalation and expansion Phase 1/2a study of oral rigosertib in combination with nivolumab in patients with KRAS+ non-small cell lung cancer, a Phase 2 program evaluating rigosertib monotherapy in advanced squamous cell carcinoma complicating recessive dystrophic epidermolysis bullosa (RDEB-associated SCC), and a Phase 2 trial evaluating rigosertib in combination with pembrolizumab in patients with metastatic melanoma.
Robert LeBoyer, Senior Vice President, Equity Research Analyst, Biotechnology, Noble Capital Markets, Inc.
Refer to the full report for the price target, fundamental analysis, and rating.
Incremental Progress Reported During 2Q23. Onconova reported a 2Q23 loss of $4.3 million or $(0.20) per share. R&D expense of $2.5 million was lower than our estimate of $4.5 million, attributed to previous completion of clinical trial start-up costs. We expect clinical costs to rise in coming quarters as patients are accrued and have adjusted our quarterly estimates. We now expect the $29.7 million cash balance to last through 2Q24.
Narazaciclib Makes Progress In Endometrial Cancer. A Phase 1/2 clinical trial testing the combination of narazaciclib with letrozole (Femara, from Novartis) in LGEEC (low grade endometrioid endometrial cancer) began treating patients in 1Q23. Onconova plans to announce results in 4Q23 including safety, pharmacokinetics, and a recommended Phase 2 dose. The Phase 2 trial is planned for 1H24 as a randomized trial against standard therapy.
Equity Research is available at no cost to Registered users of Channelchek. Not a Member? Click ‘Join’ to join the Channelchek Community. There is no cost to register, and we never collect credit card information.
This Company Sponsored Research is provided by Noble Capital Markets, Inc., a FINRA and S.E.C. registered broker-dealer (B/D).
*Analyst certification and important disclosures included in the full report. NOTE: investment decisions should not be based upon the content of this research summary. Proper due diligence is required before making any investment decision.
For a small percentage of cancer patients, doctors are unable to determine where their cancer originated. This makes it much more difficult to choose a treatment for those patients, because many cancer drugs are typically developed for specific cancer types.
A new approach developed by researchers at MIT and Dana-Farber Cancer Institute may make it easier to identify the sites of origin for those enigmatic cancers. Using machine learning, the researchers created a computational model that can analyze the sequence of about 400 genes and use that information to predict where a given tumor originated in the body.
Using this model, the researchers showed that they could accurately classify at least 40 percent of tumors of unknown origin with high confidence, in a dataset of about 900 patients. This approach enabled a 2.2-fold increase in the number of patients who could have been eligible for a genomically guided, targeted treatment, based on where their cancer originated.
“That was the most important finding in our paper, that this model could be potentially used to aid treatment decisions, guiding doctors toward personalized treatments for patients with cancers of unknown primary origin,” says Intae Moon, an MIT graduate student in electrical engineering and computer science who is the lead author of the new study.
Mysterious Origins
In 3 to 5 percent of cancer patients, particularly in cases where tumors have metastasized throughout the body, oncologists don’t have an easy way to determine where the cancer originated. These tumors are classified as cancers of unknown primary (CUP).
This lack of knowledge often prevents doctors from being able to give patients “precision” drugs, which are typically approved for specific cancer types where they are known to work. These targeted treatments tend to be more effective and have fewer side effects than treatments that are used for a broad spectrum of cancers, which are commonly prescribed to CUP patients.
“A sizeable number of individuals develop these cancers of unknown primary every year, and because most therapies are approved in a site-specific way, where you have to know the primary site to deploy them, they have very limited treatment options,” Gusev says.
Moon, an affiliate of the Computer Science and Artificial Intelligence Laboratory who is co-advised by Gusev, decided to analyze genetic data that is routinely collected at Dana-Farber to see if it could be used to predict cancer type. The data consist of genetic sequences for about 400 genes that are often mutated in cancer. The researchers trained a machine-learning model on data from nearly 30,000 patients who had been diagnosed with one of 22 known cancer types. That set of data included patients from Memorial Sloan Kettering Cancer Center and Vanderbilt-Ingram Cancer Center, as well as Dana-Farber.
The researchers then tested the resulting model on about 7,000 tumors that it hadn’t seen before, but whose site of origin was known. The model, which the researchers named OncoNPC, was able to predict their origins with about 80 percent accuracy. For tumors with high-confidence predictions, which constituted about 65 percent of the total, its accuracy rose to roughly 95 percent.
After those encouraging results, the researchers used the model to analyze a set of about 900 tumors from patients with CUP, which were all from Dana-Farber. They found that for 40 percent of these tumors, the model was able to make high-confidence predictions.
The researchers then compared the model’s predictions with an analysis of the germline, or inherited, mutations in a subset of tumors with available data, which can reveal whether the patients have a genetic predisposition to develop a particular type of cancer. The researchers found that the model’s predictions were much more likely to match the type of cancer most strongly predicted by the germline mutations than any other type of cancer.
Guiding Drug Decisions
To further validate the model’s predictions, the researchers compared data on the CUP patients’ survival time with the typical prognosis for the type of cancer that the model predicted. They found that CUP patients who were predicted to have cancer with a poor prognosis, such as pancreatic cancer, showed correspondingly shorter survival times. Meanwhile, CUP patients who were predicted to have cancers that typically have better prognoses, such as neuroendocrine tumors, had longer survival times.
Another indication that the model’s predictions could be useful came from looking at the types of treatments that CUP patients analyzed in the study had received. About 10 percent of these patients had received a targeted treatment, based on their oncologists’ best guess about where their cancer had originated. Among those patients, those who received a treatment consistent with the type of cancer that the model predicted for them fared better than patients who received a treatment typically given for a different type of cancer than what the model predicted for them.
Using this model, the researchers also identified an additional 15 percent of patients (2.2-fold increase) who could have received an existing targeted treatment, if their cancer type had been known. Instead, those patients ended up receiving more general chemotherapy drugs.
“That potentially makes these findings more clinically actionable because we’re not requiring a new drug to be approved. What we’re saying is that this population can now be eligible for precision treatments that already exist,” Gusev says.
The researchers now hope to expand their model to include other types of data, such as pathology images and radiology images, to provide a more comprehensive prediction using multiple data modalities. This would also provide the model with a comprehensive perspective of tumors, enabling it to predict not just the type of tumor and patient outcome, but potentially even the optimal treatment.
Alexander Gusev, an associate professor of medicine at Harvard Medical School and Dana-Farber Cancer Institute, is the senior author of the paper, which appeared on August 7, 2023, in Nature Medicine.
Immune Cells that Fight Cancer Become Exhausted Within Hours of First Encountering Tumors
A key function of our immune system is to detect and eliminate foreign pathogens such as bacteria and viruses. Immune cells like T cells do this by distinguishing between different types of proteins within cells, which allows them to detect the presence of infection or disease.
A type of T cell called cytotoxic T cells can recognize the mutated proteins on cancer cells and should therefore be able to kill them. However, in most patients, cancer cells grow unchecked despite the presence of T cells.
The current explanation scientists have as to why T cells fail to eliminate cancer cells is because they become “exhausted.” The idea is that T cells initially function well when they first face off against cancer cells, but gradually lose their ability to kill the cancer cells after repeated encounters.
Cancer immunotherapies such as immune checkpoint inhibitors and CAR-T cell therapy have shown remarkable promise by inducing long-lasting remission in some patients with otherwise incurable cancers. However, these therapies often fail to induce long-term responses in most patients, and T cell exhaustion is a major culprit.
This article was republished with permission from The Conversation, a news site dedicated to sharing ideas from academic experts. It represents the research-based findings and thoughts of Mary Philip, Assistant Professor of Medicine and Pathology, Vanderbilt University and Michael Rudloff, MD-Ph.D. Candidate in Molecular Pathology and Immunology, Vanderbilt University.
We are researchers who study ways to harness the immune system to treat cancer. Scientists like us have been working to determine the mechanisms controlling how well T cells function against tumors. In our newly published research, we found that T cells become exhausted within hours after encountering cancer cells.
Timing T Cell Exhaustion
By the time most patients are diagnosed with cancer, their immune system has been interacting with developing cancer cells for months to years. We wanted to go back earlier in time to figure out what happens when T cells first encounter tumor cells.
To do this, we used mice genetically engineered to develop liver cancers as they age, similarly to how liver cancers develop in people. We introduced trackable cytotoxic T cells that specifically recognize liver cancer cells to analyze the T cells’ function and monitor which of the genes are activated or turned off over time.
We also used these same trackable T cells to study their response in mice infected with the bacteria Listeria. In these mice, we found that the T cells were highly functional and eliminated infected cells. By comparing the differences between dysfunctional T cells from tumors and highly functional T cells from infected mice, we can home in on the genes that code for critical proteins that T cells use to regulate their function.
In our previous work, we found that T cells become dysfunctional with dramatically altered genetic structure within five days of encountering cancer cells in mice. We had originally decided to focus on the very earliest time points after T cells encounter cancer cells in mice with liver cancer or metastatic melanoma because we thought there would be fewer genetic changes. That would have allowed us to identify the earliest and most critical regulators of T cell dysfunction.
Instead, we found multiple surprising hallmarks of T cell dysfunction within six to 12 hours after they encountered cancer cells, including thousands of changes in genetic structure and gene expression.
T cells play an important role in fighting against disease. National Institute of Allergy and Infectious Diseases
We analyzed the different regulatory genes and pathways in T cells encountering cancer cells compared to those of T cells encountering infected cells. We found that genes associated with inflammation were highly activated in T cells interacting with infected cells but not in T cells interacting with cancer cells.
Next, we looked at how the initial early changes to the genetic structure of T cells evolved over time. We found that very early DNA changes were stabilized and reinforced with continued exposure to cancer cells, effectively “imprinting” dysfunctional gene expression patterns in the T cells. This meant that when the T cells were removed from the tumors after five days and transferred to tumor-free mice, they still remained dysfunctional.
Boosting T Cell Killing
Altogether, our research suggests that T cells in tumors are not necessarily working hard and getting exhausted. Rather, they are blocked right from the start. This is because the negative signals cancer cells send out to their surrounding environment induce T cell dysfunction, and a lack of positive signals like inflammation results in a failure to kick T cells into high gear.
Our team is now exploring strategies to stimulate inflammatory pathways in T cells encountering cancer cells to make them function as though they are encountering an infection. Our hope is that this will help T cells kill their cancer targets more effectively.
PDS Biotech is a clinical-stage immunotherapy company developing a growing pipeline of molecularly targeted cancer and infectious disease immunotherapies based on the Company’s proprietary Versamune® and Infectimune™ T-cell activating technology platforms. Our Versamune®-based products have demonstrated the potential to overcome the limitations of current immunotherapy by inducing in vivo, large quantities of high-quality, highly potent polyfunctional tumor specific CD4+ helper and CD8+ killer T-cells. PDS Biotech has developed multiple therapies, based on combinations of Versamune® and disease-specific antigens, designed to train the immune system to better recognize diseased cells and effectively attack and destroy them. The Company’s pipeline products address various cancers including HPV16-associated cancers (anal, cervical, head and neck, penile, vaginal, vulvar) and breast, colon, lung, prostate and ovarian cancers.
Robert LeBoyer, Senior Vice President, Equity Research Analyst, Biotechnology, Noble Capital Markets, Inc.
Refer to the full report for the price target, fundamental analysis, and rating.
First Data From Prostate Cancer. PDS announced that it will present interim data from its first trial testing PDS301 with docetaxel (Taxotere) in prostate cancer patients. The presentation will be at the International Cytokine and Interferon Society annual meeting in October 2023. We see acceptance of the PDS0301 data for presentation as positive sign for proof-of-concept and expansion into new indications.
Data Will Be From A Dose-Finding Trial To Establish Responses and Safety. The trial tests the combination of PDS0301 with docetaxel in metastatic prostate cancer. The regimen was given in 3-week cycles consisting of a standard dose of docetaxel with one of three dose levels of PDS0301. The presentation abstract is based on safety, immune responses, and clinical activity data from 18 patients.
Equity Research is available at no cost to Registered users of Channelchek. Not a Member? Click ‘Join’ to join the Channelchek Community. There is no cost to register, and we never collect credit card information.
This Company Sponsored Research is provided by Noble Capital Markets, Inc., a FINRA and S.E.C. registered broker-dealer (B/D).
*Analyst certification and important disclosures included in the full report. NOTE: investment decisions should not be based upon the content of this research summary. Proper due diligence is required before making any investment decision.
PDS Biotech is a clinical-stage immunotherapy company developing a growing pipeline of molecularly targeted cancer and infectious disease immunotherapies based on the Company’s proprietary Versamune® and Infectimune™ T-cell activating technology platforms. Our Versamune®-based products have demonstrated the potential to overcome the limitations of current immunotherapy by inducing in vivo, large quantities of high-quality, highly potent polyfunctional tumor specific CD4+ helper and CD8+ killer T-cells. PDS Biotech has developed multiple therapies, based on combinations of Versamune® and disease-specific antigens, designed to train the immune system to better recognize diseased cells and effectively attack and destroy them. The Company’s pipeline products address various cancers including HPV16-associated cancers (anal, cervical, head and neck, penile, vaginal, vulvar) and breast, colon, lung, prostate and ovarian cancers.
Robert LeBoyer, Senior Vice President, Equity Research Analyst, Biotechnology, Noble Capital Markets, Inc.
Refer to the full report for the price target, fundamental analysis, and rating.
The Phase 2 VERSATILE-002 Trial Remains Misunderstood. We have received inquiries from investors about the data in the recent ASCO presentation by PDS Biotech. We believe there is some misunderstanding of the trial design, outcome data, and the trial’s definition of efficacy. In view of the fundamental progress and stock price decline, we believe this is a buying opportunity.
Trial Data Has Led To Misinterpretation. The Phase 2 VERSATILE-002 trial has a primary endpoint of best overall response rate (ORR). To be considered a responder, patients need to have tumor shrinkage of at least 30% in two MRI scans. Patients with one positive scan are considered unconfirmed responses until they have a second confirming scan at least 9 weeks later. Both confirmed and unconfirmed responses were reported at the recent ASCO conference.
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This Company Sponsored Research is provided by Noble Capital Markets, Inc., a FINRA and S.E.C. registered broker-dealer (B/D).
*Analyst certification and important disclosures included in the full report. NOTE: investment decisions should not be based upon the content of this research summary. Proper due diligence is required before making any investment decision.
PDS Biotech is a clinical-stage immunotherapy company developing a growing pipeline of molecularly targeted cancer and infectious disease immunotherapies based on the Company’s proprietary Versamune® and Infectimune™ T-cell activating technology platforms. Our Versamune®-based products have demonstrated the potential to overcome the limitations of current immunotherapy by inducing in vivo, large quantities of high-quality, highly potent polyfunctional tumor specific CD4+ helper and CD8+ killer T-cells. PDS Biotech has developed multiple therapies, based on combinations of Versamune® and disease-specific antigens, designed to train the immune system to better recognize diseased cells and effectively attack and destroy them. The Company’s pipeline products address various cancers including HPV16-associated cancers (anal, cervical, head and neck, penile, vaginal, vulvar) and breast, colon, lung, prostate and ovarian cancers.
Robert LeBoyer, Senior Vice President, Equity Research Analyst, Biotechnology, Noble Capital Markets, Inc.
Refer to the full report for the price target, fundamental analysis, and rating.
ASCO Efficacy Data Has Been Updated. PDS Bioscience announced that the Phase 2 VERSATILE-002 trial has met the threshold for efficacy. This is good news for the trial and should help clarify misunderstandings of the data presented at the ASCO conference earlier this month. The Phase 3 trial is expected to begin in 3Q23.
New Data Should Clarify Trial Results. In our June Research Note, we discussed data from the VERSATILE-002 trial presented at the ASCO annual meeting. This presentation showed a 12-month survival rate of 87% and a progression-free survival rate of 10.4 months. Responses were determined by the RECIST 1.1 criteria, requiring 30% tumor shrinkage. According to the trial protocols, responses seen in the first scan were considered unconfirmed responses until a second confirmatory scan 9 weeks later.
Equity Research is available at no cost to Registered users of Channelchek. Not a Member? Click ‘Join’ to join the Channelchek Community. There is no cost to register, and we never collect credit card information.
This Company Sponsored Research is provided by Noble Capital Markets, Inc., a FINRA and S.E.C. registered broker-dealer (B/D).
*Analyst certification and important disclosures included in the full report. NOTE: investment decisions should not be based upon the content of this research summary. Proper due diligence is required before making any investment decision.
