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Kairos Pharma’s stock had a bumpy ride on its first day trading, shedding 35% of its value to end Monday down at $2.60. With a trio of biotechs hitting the Nasdaq on Friday, it was easy to miss a smaller-scale public debut from another clinical-stage drug developer on the other side of the European Society of Medical Oncology annual meeting this weekend.Unlike last week’s nine-figure offerings, Kairos Pharma’s IPO brought in a more modest $6.2 million yesterday. The Los Angeles-based biotech—whose stock listed on the NYSE under the ticker “KAPA” Sept. 16—sold 1.55 million shares at $4 apiece.Underwriters have 45 days to buy an additional 232,500 shares at the same price, which could bring in another $930,000, the company explained in a Sept. 16 release.The top priority for spending the IPO proceeds is the biotech’s lead candidate ENV 105, an endoglin-targeting monoclonal antibody that the company said is designed to “reverse resistance to standard-of-care drugs.”Kairos is already assessing ENV 105 in a phase 1 trial for non-small cell lung cancer in combination with AstraZeneca’s Tagrisso, as well as a phase 2 prostate cancer study in combination with Johnson & Johnson’s Erleada. Behind ENV 105 are preclinical candidates like KROS 101, a small molecule agonist for the GITR ligand, which is designed to promote T cell growth and cytotoxic function against cancer.  There’s also ENV 205, an antibody that targets mitochondrial DNA that’s elevated as patients become resistant to chemotherapies.Kairos' stock had a bumpy ride on its first day of trading, shedding 35% of its value to end Monday down at $2.60.It’s a stark contrast to the three biotech Nasdaq IPOs on Friday, which all experienced a warmer reception on the public markets. Bicara Therapeutics' $315 million offering was the largest IPO of the day, and the company saw its $18 debut share price jump 41% to $25.41 by close of trading Monday. Meanwhile, MBX was trading up 26% at $21.65, and Zenas BioPharma was trading up 5% at $17.90 by the same point.Kairos launched as a spinout from the Cedars-Sinai Medical Center in 2013 before merging with AcTcell Biopharma in 2019. Two years later, the biotech also absorbed Enviro Therapeutics, which had been developing ENV 105.

In a recent trial, nine patients whose tumors were resistant to androgen-blocking therapy continued that therapy but were also given a CD105 inhibitor called carotuximab. Forty percent of those patients experienced progression-free survival, based on radiographic imaging Investigators from Cedars-Sinai Cancer have identified an investigational therapeutic approach that could be effective against treatment-resistant prostate cancer. Results of their Phase II clinical trial, published in the peer-reviewed journal Molecular Therapy, have led to a larger, multicenter trial that will soon be underway. Cancer of the prostate, a small gland just below the bladder, is the second-leading cause of cancer-related death in men. Many prostate tumors are not aggressive and may require no or minimal treatment. Aggressive tumors are initially treated with surgery or radiation therapy. In about one-third of patients, the cancer comes back after initial treatment, said Neil Bhowmick, PhD, research scientist at Cedars-Sinai Cancer, professor of Medicine and Biomedical Sciences and senior author of the study. Those patients are usually treated with medications that suppress the actions of testosterone and other androgens -- male hormones that help prostate tumors grow. "Patients do really well until the tumor figures a way around the androgen-suppressing therapy," Bhowmick said. "One way that it can do this is to cause cells to make only part of the protein that the drug binds to, rendering the drug useless. The partial proteins are called splice variants." Through research with human cells and laboratory mice, study first author Bethany Smith, PhD, a project scientist in the Bhowmick Lab, figured out that the cancer cells were signaling to the surrounding supportive cells through a protein called CD105 to make these slice variant proteins. Investigators then conducted a trial in human patients to test a drug that they hoped would keep those partial proteins from forming by inhibiting CD105. In the trial, nine patients whose tumors were resistant to androgen-blocking therapy continued that therapy but were also given a CD105 inhibitor called carotuximab. Forty percent of those patients experienced progression-free survival, based on radiographic imaging. "Every single one of the patients in our trial was totally resistant to at least one androgen suppressor, and the normal course of action would be to simply try a different one or chemotherapy, which research has shown generally doesn't stop tumor growth for more than about three months," Bhowmick said. "Carotuximab prevented the cancer's workaround and made the tumor sensitive to androgen-suppressing therapy." Importantly, Bhowmick said, carotuximab also appears to prevent androgen receptor splice variants in the supporting cells surrounding tumors, further sensitizing the tumor to the androgen suppressor. "We found that this therapy may be able to, especially in early cancers, resensitize select patients to androgen suppression. This could allow patients to avoid or delay more toxic interventions such as cytotoxic chemotherapy," said Edwin Posadas, MD, co-director of the Experimental Therapeutics Program, medical director of the Urologic Oncology Program/Center for Uro-Oncology Research Excellence (CURE), associate professor of Medicine at Cedars-Sinai and a co-author of the study. "We also hope to find ways of predicting which patients are most likely to benefit from this approach by testing blood and tissue samples using next-generation technologies housed at Cedars-Sinai Cancer." Study co-author Sungyong You, PhD, director of the Urologic Oncology Bioinformatics Group, pinpointed three biomarkers that could help indicate which patients will respond to this investigational therapy, and the team will validate those markers in a new clinical trial. This will allow future studies to target patients most likely to be helped by this intervention, Bhowmick said. Funding: The study was supported by Department of Defense grant number W81XWH-17-1-0154 and Veterans Administration grant number I01BX001040.

Kairos Pharma, Ltd. ("Kairos"), a privately held clinical stage biotechnology company focused on drug resistance and immunotherapy for cancer, today announced that it has received FDA approval to proceed with a Phase 2 clinical trial of ENV105 with apalutamide for the treatment of metastatic castration-resistant prostate cancer. The phase II trial is sponsored by Enviro Therapeutics, a wholly-owned subsidiary of Kairos Pharma. Kairos CEO John Yu, M.D. commented, "This IND acceptance establishes the first of many substantial clinical milestones that Kairos is working toward in 2022. We will roll out our Phase 2 clinical trial with the goal of verifying the benefit of our transformative technologies to reverse the normal course of drug resistance in patients with prostate cancer, lung cancer, and breast cancer." ENV105 has been demonstrated to complement standard of care androgen targeted therapy with non-steroidal anti-androgens such as XTANDI® (enzalutamide) and Zytiga® (abiraterone acetate) in limiting therapeutic resistance to these drugs in a previous Phase II trial. These encouraging results is the premise for this randomized, multi-center phase II trial enrolling 100 patients. Prostate cancer patients failing to respond to androgen targeted therapy interventions will be randomized to receive the combination of ENV105 and a third-generation androgen receptor antagonist, apalutamide or apalutamide alone. Interruption of the BMP/CD105 signaling between cancer cells and surrounding non-cancer cells with ENV105 sensitizes prostate tumors to androgen targeted therapy through a novel mechanism of action. Three academic medical centers will participate in the randomized trial including Cedars Sinai Medical Center, University of Utah, and City of Hope. Kairos Chief Scientific Officer Neil Bhowmick, Ph.D. added, "This achievement represents the next major step in testing the degree of potential clinical benefit of ENV105 for patients with androgen resistant prostate cancer." In addition to the upcoming Phase 2 trial of ENV105 with apalutamide, a Phase 1 trial of ENV105 with Tagrisso (AstraZeneca) for lung cancer is planned to start in 2022, and a Phase 1 trial of activated T cell therapy for KROS 201 in patients with glioblastoma will enter Phase 1 clinical trials in 2022. About Kairos Pharma Kairos Pharma is a clinical-stage biopharmaceutical company focused on developing a diversified pipeline of cutting-edge therapeutics for cancer patients that reverse the inhibitory effects of cancer on the immune system. The Company's unique portfolio of seven drug candidates is anchored by a new class of novel drugs that reverse drug resistance and immune resistance to cancer. The Company has made unparalleled strides through its transformative technology, strong IP, and world-class team working to make a significant impact on the most pervasive problems in cancer treatment.