On February 14, 2022 Primmune Therapeutics, a biotech company harnessing the power of the innate immune system to treat cancers and viral diseases, reported that interim data related to PRTX007, a novel, orally administered, small molecule toll-like receptor 7 (TLR7) specific agonist that is currently in Phase 1 development, at the Conference on Retroviruses and Opportunistic Infections (CROI) (Press release, Primmune Therapeutics, FEB 14, 2022, View Source [SID1234608058]). Oral administration of PRTX007 in this first-in-human study of healthy volunteers exhibited a favorable safety profile, rapid absorption and conversion to TLR7 agonist PRX034, and activation of the innate immune system, without causing inflammation.

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"PRTX007 is being developed to harness the power of the innate immune system by targeting TLR7, without increasing cytokines that can result in hyperinflammation and can harm patients," said James Appleman, Ph.D., Co-Founder and Chief Scientific Officer at Primmune Therapeutics. "We look forward to continuing the development of PRTX007 to address current unmet needs of patients with cancers and viral infections."

Highlights of this data, presented in a poster titled "Interim Analysis of a Phase 1 Study of PRTX007: Safety, PK, and PD Response," include:

Oral administration of PRTX007 resulted in efficient systemic delivery and well-behaved pharmacokinetics of agonist PRX034
TLR7-mediated immune response was shown to be dose and exposure-dependent
TLR7-mediated immune induction of IFN-gene products and other TLR7-associated cytokines was observed without increases in NF-κB mediated biosynthesis of proinflammatory cytokines IL-6, TNF⍺, IL-1β
Data demonstrate a favorable safety profile for PRTX007
Full details of the presentation can be found here.

About PRTX007

PRTX007 is Primmune’s lead TherAjuvant, a combination of therapeutic and adjuvant mechanisms of action. PRTX007 is designed to provide immediate benefit to patients through controlled stimulation of the innate immune response while also potentiating long-term effective innate and adaptive immune responses. PRTX007 uniquely engages TLR7 and targeted immune cells without increasing levels of proinflammatory factors like IL-6, TNFα and IL-1β via NF-κB. TherAjuvants differ from other small molecule approaches in that they engage the patient’s immune system rather than acting at virally encoded targets or endogenous tumor cell proteins. PRTX007 is being rapidly advanced towards clinical trials for cancer and viral diseases.

On February 14, 2022 AVEO Oncology (Nasdaq: AVEO), a commercial stage, oncology-focused biopharmaceutical company, reported that new long-term progression free survival (PFS) data from the Phase 3 TIVO-3 study, which compares FOTIVDA (tivozanib) to Nexavar (sorafenib) in advanced renal cell carcinoma (RCC) patients following two or more prior systemic therapies, are being presented at the 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Genitourinary (ASCO GU) Cancers Symposium being held in San Francisco on February 17th – 19th (Press release, AVEO, FEB 14, 2022, View Source [SID1234608074]).

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"The long-term PFS data we are presenting at the ASCO (Free ASCO Whitepaper) GU meeting this week further strengthen the body of data supporting FOTIVDA as a potential standard of care in third- and fourth-line RCC treatment. This marks the first presentation of five year follow-up data for patients being treated in the third- or fourth-line RCC setting and helps guide clinical treatment," said Michael Bailey, President and Chief Executive Officer of AVEO. "We are excited to report that the five year follow-up data announced today show that patients receiving FOTIVDA are up to five times more likely to experience long-term progression free survival as compared to sorafenib. Long-term follow-up of the TIVO-3 study suggests early and consistent PFS benefit with FOTIVDA ultimately may be associated with the trend toward improved overall survival."

ASCO GU 2022 TIVO-3 Phase 3 Five Year Follow-up Data include:

Investigator-assessment of PFS with long-term follow-up for TIVO-3 is consistent with the primary independent review committee.
Landmark five year follow-up data show PFS rates are consistently higher with FOTIVDA vs. sorafenib, with 12% vs. 2% and 8% vs. 0% at three and four years, respectively. Long-term PFS represents a clinically meaningful outcome for patients in the third- and fourth-line treatment setting.
Long term OS was also analyzed, and a non significant trend favoring FOTIVDA continued to emerge with accumulation of events (HR, 0.89).
ASCO GU 2022 Poster/Abstract Details:
Title: Long-term PFS from TIVO-3: Tivozanib (TIVO) vs. sorafenib (SOR) in relapsed/refractory (R/R) advanced RCC
First Author: Michael B. Atkins MD
Abstract: 362
Track: Renal Cell Cancer
Date and Time: February 19, 2022 at 10 a.m. Eastern Time

Details on the presentation are available on the 2022 ASCO (Free ASCO Whitepaper) GU website (click here). The poster scheduled to be presented at the 2022 ASCO (Free ASCO Whitepaper) GU Cancers Symposium will be available on the Publications page of the AVEO Oncology website (click here) subsequent to the presentation.

About FOTIVDA (tivozanib)

FOTIVDA (tivozanib) is an oral, next-generation vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor (TKI). It is a potent, selective inhibitor of VEGFRs 1, 2, and 3 with a long half-life designed to improve efficacy and tolerability. AVEO received U.S. Food and Drug Administration (FDA) approval for FOTIVDA on March 10, 2021 for the treatment of adult patients with relapsed or refractory advanced renal cell carcinoma (RCC) following two or more prior systemic therapies. FOTIVDA was approved in August 2017 in the European Union and other countries in the territory of its partner EUSA Pharma (UK) Limited for the treatment of adult patients with advanced RCC. FOTIVDA has been shown to significantly reduce regulatory T-cell production in preclinical models.2 FOTIVDA was discovered by Kyowa Kirin.

INDICATIONS

FOTIVDA is indicated for the treatment of adult patients with relapsed or refractory advanced renal cell carcinoma (RCC) following two or more prior systemic therapies.

IMPORTANT SAFETY INFORMATION

WARNINGS AND PRECAUTIONS

Hypertension and Hypertensive Crisis: Control blood pressure prior to initiating FOTIVDA. Monitor for hypertension and treat as needed. For persistent hypertension despite use of anti-hypertensive medications, reduce the FOTIVDA dose.

Cardiac Failure: Monitor for signs or symptoms of cardiac failure throughout treatment with FOTIVDA.

Cardiac Ischemia and Arterial Thromboembolic Events: Closely monitor patients who are at increased risk for these events. Permanently discontinue FOTIVDA for severe arterial thromboembolic events, such as myocardial infarction and stroke.

Venous Thromboembolic Events: Closely monitor patients who are at increased risk for these events. Permanently discontinue FOTIVDA for severe venous thromboembolic events.

Hemorrhagic Events: Closely monitor patients who are at risk for or who have a history of bleeding.

Proteinuria: Monitor throughout treatment with FOTIVDA. For moderate to severe proteinuria, reduce the dose or temporarily interrupt treatment with FOTIVDA.

Thyroid Dysfunction: Monitor before initiation and throughout treatment with FOTIVDA.

Risk of Impaired Wound Healing: Withhold FOTIVDA for at least 24 days before elective surgery. Do not administer for at least 2 weeks following major surgery and adequate wound healing. The safety of resumption of FOTIVDA after resolution of wound healing complications has not been established.

Reversible Posterior Leukoencephalopathy Syndrome (RPLS): Discontinue FOTIVDA if signs or symptoms of RPLS occur.

Embryo-Fetal Toxicity: Can cause fetal harm. Advise patients of the potential risk to a fetus and to use effective contraception.

Allergic Reactions to Tartrazine: The 0.89 mg capsule of FOTIVDA contains FD&C Yellow No.5 (tartrazine) which may cause allergic-type reactions (including bronchial asthma) in certain susceptible patients.

ADVERSE REACTIONS

The most common (≥20%) adverse reactions were fatigue, hypertension, diarrhea, decreased appetite, nausea, dysphonia, hypothyroidism, cough, and stomatitis, and the most common Grade 3 or 4 laboratory abnormalities (≥5%) were sodium decreased, lipase increased, and phosphate decreased.

DRUG INTERACTIONS

Strong CYP3A4 Inducers: Avoid coadministration of FOTIVDA with strong CYP3A4 inducers.

USE IN SPECIFIC POPULATIONS

Lactation: Advise not to breastfeed.
Females and Males of Reproductive Potential: Can impair fertility.
Hepatic Impairment: Adjust dosage in patients with moderate hepatic impairment. Avoid use in patients with severe hepatic impairment.

To report SUSPECTED ADVERSE REACTIONS, contact AVEO Pharmaceuticals, Inc. at 1-833-FOTIVDA (1-833-368-4832) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Please see FOTIVDA Full Prescribing Information which is available at www.FOTIVDA.com.

About Advanced Renal Cell Carcinoma

According to the American Cancer Society’s 2021 statistics, renal cell carcinoma (RCC) is the most common type of kidney cancer, which is among the ten most common cancers in both men and women. Approximately 73,750 new cases of kidney cancer will be diagnosed annually and about 14,830 people will die from this disease. In patients with late-stage disease, the five-year survival rate is 13%. Agents that target the vascular endothelial growth factor (VEGF) pathway have shown significant antitumor activity in RCC.3 According to a 2019 publication, 50% of the approximately 10,000 patients who progress following two or more lines of therapy choose not to receive further treatment,4 which may be attributable to tolerability concerns and a lack of data to support evidence-based treatment decisions in this highly relapsed or refractory patient population.

On February 14, 2022 Adcentrx Therapeutics ("Adcentrx"), a biotechnology company focused on accelerating breakthroughs in antibody drug conjugate ("ADC") therapeutic development, and AvantGen, a leader in the use of yeast display technology for human antibody discovery and optimization, reported a three-year, multi-target partnership for the discovery of antibodies to be developed into novel ADC therapeutic candidates (Press release, Adcentrx Therapeutics, FEB 14, 2022, https://www.prnewswire.com/news-releases/adcentrx-and-avantgen-enter-a-new-partnership-with-a-three-year-multi-target-collaboration-to-discover-antibodies-for-novel-antibody-drug-conjugates-301482030.html [SID1234608092]).

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Under the terms of the collaboration, Adcentrx will specify targets against which AvantGen will screen for novel antibodies using its yeast display system. Adcentrx will be responsible for engineering the antibodies into ADC therapeutic candidates and has worldwide development and commercialization rights. AvantGen will be eligible to receive milestone payments for achievement of certain development milestones.

"We are excited to enter this new partnership with AvantGen to accelerate our ADC development efforts," said Hui Li, Ph.D., President and CEO of Adcentrx. "What attracted us to AvantGen initially is how their yeast display technology and human antibody libraries mimic human diversity to yield high affinity and very specific antibodies. Through our ongoing collaboration, AvantGen has demonstrated its capabilities in rapidly discovering a diverse antibody repertoire with high developability against defined targets. A key objective at Adcentrx, through this collaboration and opportunistic licensing activities, is to identify the best antibodies which we can leverage to assemble a pipeline of next generation ADC therapeutics."

"We are proud to partner with Adcentrx to help accelerate its ADC pipeline build with our robust human antibody discovery platform," said Xiaomin Fan, Ph.D., President and CEO of AvantGen. "The speed that Adcentrx is able to take lead antibody candidates to development stage with its ADC technology is truly remarkable. We believe that this new partnership will enable Adcentrx to develop the most promising next generation ADC therapeutics with our high-quality antibodies."

On February 14, 2022 Moleculin Biotech, Inc., (Nasdaq: MBRX) ("Moleculin" or the "Company"), a clinical stage pharmaceutical company with a broad portfolio of drug candidates targeting highly resistant tumors and viruses, reported preliminary results supporting the successful conclusion of its second Phase 1 trial (MB-105) in Poland evaluating Annamycin for the treatment of relapsed and refractory acute myeloid leukemia (AML), where Moleculin determined a dose of 240 mg/m2 as the Recommended Phase 2 Dose (RP2D), subject to final approval of the Safety Review Committee, and indicated no signs of cardiotoxicity (a common problem with currently prescribed anthracyclines) (Press release, Moleculin, FEB 14, 2022, View Source [SID1234608059]). Based on preclinical animal data from sponsored research conducted simultaneous with its clinical trials, Annamycin in combination with Cytarabine demonstrated a 68% improvement in the median overall survival (OS) compared to Annamycin as a single agent and a 241% increase in OS compared to Cytarabine alone. Based on this data, the Company plans to advance its AML clinical development program in a Phase 1/2 clinical trial in Europe evaluating the combination of Annamycin and Cytarabine utilizing the clinical data from its two prior Phase 1 clinical trials.

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"This important study conclusion now allows us to combine the safety and efficacy data from our MB-104 and MB-105 AML clinical trials using Annamycin as a single agent, along with the recent findings from preclinical studies showing that the combination of Annamycin with Cytarabine (AnnAraC) has the ability to synergistically improve activity against AML and move directly into a new AML clinical trial to study AnnAraC in humans," Dr. J. Paul Waymack, Senior Chief Medical Officer of the Company, commented. He continued, "The support of local physicians in Poland for an AML trial utilizing AnnAraC is encouraging, and we believe this will translate into a faster pace of recruitment than we experienced in our MB-105 clinical trial. As such, our Annamycin AML program is now positioned to progress to a Phase 1/2 combination clinical trial in Europe as soon as possible. We expect to begin this trial in the first half of this year."

"The RP2D will assist in setting the initial dosage in the AnnAraC clinical trial but imposes no limit on Annamycin as the new clinical study will have its own Phase 1 dose escalation portion setting a new RP2D for the combination. The successful outcome of our second Phase 1 study combined with the data we have seen to-date represents a major milestone in the AML program as we believe successful Phase 2 data from the combination trial could position AnnAraC for late-stage development and faster approval in AML versus Annamycin as a single agent," added Mr. Walter Klemp, Chairman and CEO of Moleculin Biotech.

In January, the Company reported that it had received an updated independent safety review of certain preliminary data for the first 30 patients in its three Phase 1 clinical trials with Annamycin targeting AML (MB-104 and MB-105) and the metastases of soft tissue sarcoma to the lungs (STS Lung) or MB-107, which concluded there was no evidence of cardiotoxicity. Specifically, the trial Moleculin is concluding (MB-105), began its first cohort with an initial dose of 120 mg/m2 for three consecutive days. Each cohort contained three patients receiving a full course of Annamycin. In the fifth and final cohort, patients’ daily dose was 240 mg/m2 with five patients receiving a full course of Annamycin. The overall response rate (ORR) was 60% in the last cohort. This included two partial responses (PR’s) and one complete response with incomplete recovery of neutrophils and/or platelets (CRi). Upon safely reaching the RP2D of 240 mg/m2 in the MB-105 trial, the Company has concluded recruitment for the trial. The data from MB-104 and MB-105 trials will be used to design and support the new proposed combination trial.

The clinical data presented above are preliminary and subject to changes as the final clinical study report will be prepared in the near term.

The Company reported in November of 2020 new animal data from its sponsored research program showing highly improved activity against acute myeloid leukemia when Annamycin was used in combination with the commonly used antileukemic drug Cytarabine (Ara-C) versus single agent. The data was presented at the 62nd Annual Meeting & Exposition of the American Society for Hematology ("ASH") under the title: "High Efficacy of Liposomal Annamycin (L-ANN or Annamycin) in Combination with Cytarabine in Syngeneic p53-null AML Mouse Model."1 This study demonstrated vastly higher efficacy of the L-ANN/ARA-C combination (AnnAraC) over that of the single agents in an immune-competent setting of an aggressive, p53-null AML model. The study summarily demonstrated a 68% improvement in median OS of the animals in the study compared to Annamycin as a single agent and a 241% increase in OS compared to Cytarabine alone.

1 Zal T, Zielinski R, Grela K, Cardenas-Zuniga R, Skora S, Fokt I, Zal A, Andreeff M, Gil L Shephard R, Priebe W, High Efficacy of Liposomal Annamycin (L-ANN) in Combination with Cytarabine in Syngeneic p53-Null AML Mouse Model, Blood (2020) 136 (Supplement 1): 6–7. View Source

About Annamycin

Annamycin is the Company’s next-generation anthracycline that has been shown in animal models to accumulate in the lungs at up to 30-fold the level of doxorubicin. Importantly, Annamycin has also demonstrated a lack of cardiotoxicity in multiple human clinical trials, including ongoing trials for the treatment of relapsed or refractory acute myeloid leukemia (AML) and soft tissue sarcoma (STS) lung metastases, and the Company believes that the use of Annamycin may not face the same usage limitations imposed on doxorubicin, one of the most common currently prescribed anthracyclines. Annamycin is currently in development for the treatment of AML and STS lung metastases and the Company believes it may have the potential to treat a number of additional indications.

Annamycin currently has Fast Track Status and Orphan Drug Designation from the U.S. Food and Drug Administration for the treatment of STS lung metastases, in addition to Orphan Drug Designation for the treatment of relapsed or refractory acute myeloid leukemia. For more information about the Phase 1b/2 study evaluating Annamycin for the treatment of STS lung metastases, please visit clinicaltrials.gov and reference identifier NCT04887298.

On February 14, 2022 ImmunityBio, Inc. (NASDAQ: IBRX), a clinical-stage immunotherapy company, reported positive data from the company’s late-stage bladder cancer trial (QUILT-3.032) (Press release, ImmunityBio, FEB 14, 2022, View Source [SID1234608075]). The data showed sustained complete response rates in patients with BCG-unresponsive non-muscle invasive carcinoma in situ (NMIBC CIS) bladder cancer (Cohort A) and with papillary disease (Cohort B). Of the 83 patients with BCG-unresponsive NMIBC CIS, 59 (71%) had a complete response with a median duration of response of 24.1 months—exceeding historical complete response rates of 41% and 18% for FDA-approved therapies pembrolizumab and valrubicin, respectively. In the papillary disease arm of the study (Cohort B), 57% of patients are disease free at 12 months and 53% at 18 months.

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"We are excited with these promising results," said Sam Chang, M.D., Urologic Surgery Chief Surgical Officer, Vanderbilt Ingram Cancer Center and trial investigator. "This study suggests that BCG induces trained immunity as the prime, while N-803 serves as a vital boost for innate immune memory. These results of high efficacy activity and excellent safety profile set a new bar for NMIBC treatment, and together with the familiar and favorable mode of administration, will advance our current standards of care for patients with bladder cancer."

The latest data from this trial exceeds AUA-FDA workshop benchmarks for both the magnitude of complete remission and the duration of complete response for new therapies for BCG-unresponsive bladder cancer. Indeed, the benchmark of 30% durable response at 18 to 24 months for a clinically meaningful therapy "is likely too high and may not be realistically achievable,"3 according to recommendations published in the Journal of Clinical Oncology. This "realistically unachievable" endpoint of 30% durable response at 18 months has in fact now been achieved and exceeded with the combination of Anktiva and BCG in this trial reported today. Taken together, the high rates of complete response, cystectomy avoidance, avoidance of progression to muscle invasive disease in the patients that responded, and the prolonged duration of complete response, as well as the favorable safety profile, places this novel immunotherapy combination at the forefront of both existing approved and potential treatments for bladder cancer patients.

"Trained immunity is a recently discovered immune system response triggered by BCG. Natural Killer (NK) and T cells are activated by BCG resulting in bladder cancer cell death. When an appropriate secondary stimulus is administered along with BCG, that trained immune response is enhanced to induce immune memory resulting in a prolonged duration of immunological response," said Patrick Soon-Shiong, M.D., Executive Chairman and Global Chief Scientific and Medical Officer of ImmunityBio. "N-803, our IL-15 superagonist which proliferates NK and T cells, serves as this enhancing secondary boost and augments the immunological response when given in combination with BCG. This mechanism of action of inducing trained innate immune memory, through the combination of N-803 and BCG, accounts for the prolonged 24-month durable complete response reported in this trial."

"These results support our hypothesis that immunogenic cell death can induce long-term memory and that N-803 increases the immunologic potential of BCG, even in patients who become unresponsive to BCG alone," Soon-Shiong said. "N-803 does this by stimulating proliferation and enhancing activity of tumor-killing Natural Killer (NK) cells and T cells, acting as a secondary stimulus or boost to the prime trained immunity induced by BCG."

The study results presented at ASCO (Free ASCO Whitepaper) GU are summarized below:

Cohort A (CIS)
Excellent safety and tolerability profile of N-803 + BCG for CIS

0% treatment-related SAEs
0% immune-related AE
0% grade 4 and 5 AE
71% Complete remission (CR) rate at anytime
24.1 Months median durable complete remission
96% Avoidance of bladder cancer progression at 24 months in responders
91% Avoidance of cystectomy at 24 months in responders
100% Bladder cancer specific overall survival at 24 months
Favorable & familiar dosing schedule with activity localized to the bladder
Cohort B (Papillary Disease)
Excellent safety and tolerability profile of N-803 + BCG for papillary disease

0% treatment-related SAEs
0% immune-related AE
0% grade 4 and 5 AE
57% Disease free survival rate at 12 months
99% Overall bladder cancer specific survival
95% Cystectomy avoidance rate
Favorable & familiar dosing schedule with activity localized to the bladder
"When we began the QUILT trials across multiple tumor types, initiating our Cancer Moonshot program, the goal was to achieve a new paradigm in cancer care by activating the patient’s own immune system to induce NK and T cell memory with long-term complete remission in patients who have failed all current therapies," Soon-Shiong said. "With these results in bladder cancer, as well as our recently reported results in pancreatic cancer, we are one step closer to proving our hypothesis that delivering therapies that harness the patient’s own immune system is what will truly transform current standards of care."

The data will be announced on Friday, February 18 during an oral presentation at the 2022 ASCO (Free ASCO Whitepaper) Genitourinary Cancers Symposium titled Phase II/III clinical results of IL-15RαFc superagonist N-803 with BCG in BCG-unresponsive non-muscle invasive bladder cancer (NMIBC)

Incidence of Bladder Cancer

Bladder cancer has a high incidence worldwide; in 2020, an estimated 573,278 new cases were diagnosed and caused 212,536 deaths.4 In the United States, bladder cancer is the fourth most commonly-diagnosed solid malignancy in men and the twelfth for women; the American Cancer Society estimates there will be 83,730 new cases and 17,200 deaths from bladder cancer in 2021.5 Approximately 75–85% of bladder cancer patients present with a disease confined to the mucosa (stage Ta, carcinoma in situ) or submucosa (stage T1); these categories are grouped as non-muscle-invasive bladder cancer (NMIBC). Of these, approximately 70% present as stage Ta, 20% as T1, and 10% as CIS.6

For the last 30 years, BCG immunotherapy has been the standard for treating NMIBC. However, disease recurrence and progression rates remain unacceptably high. Standard-of-care recommendations include lifetime invasive surveillance and rapid treatment of recurrences, creating a substantial financial burden and drastic impact on quality of life. Of those patients who experience recurrence, approximately 30% will succumb to their disease over a 15-year period, and another 50% will undergo radical cystectomy of the bladder (surgical removal of the bladder that may require removing surrounding organs) in an attempt to control the disease.7

There is an urgent, unmet need to treat NMIBC and avoid cystectomy. Despite the advent of minimally-invasive procedures and robotic techniques, the 90-day mortality and morbidity rates in cystectomy patients remain unacceptably high at 3-6% and 28-64%, respectively.8&9 Based on this urgent need, the FDA published guidance in February 2018 to address BCG unresponsive NMIBC, stating that the goal of therapy in patients with BCG-unresponsive NMIBC is to avoid cystectomy.

About the Study and Breakthrough Designation

QUILT 3.032 is an open-label, three cohort, multicenter Phase 2/3 study of intravesical BCG plus Anktiva (N-803) in patients with BCG-unresponsive high-grade NMIBC (NCT03022825) and was opened in 2017. The primary endpoint for Cohort A of this Phase 2/3 study is incidence of complete response (CR) of CIS at any time. The FDA had granted Fast Track Designation to the pivotal trial based on Phase I data. In December 2019, the FDA granted ImmunityBio Breakthrough Therapy Designation based on interim Phase 2 data indicating the primary endpoint of the trial was already met.

ImmunityBio’s IL-15 superagonist Anktiva (N-803)

The cytokine interleukin-15 (IL-15) plays a crucial role in the immune system by affecting the development, maintenance, and function of the natural killer (NK) and T cells. N-803 is a novel IL-15 superagonist complex consisting of an IL-15 mutant (IL-15N72D) bound to an IL-15 receptor α/IgG1 Fc fusion protein. Its mechanism of action is direct specific stimulation of CD8+ T cells and NK cells through beta gamma T-cell receptor binding (not alpha) while avoiding T-reg stimulation. N-803 has improved pharmacokinetic properties, longer persistence in lymphoid tissues and enhanced anti-tumor activity compared to native, non-complexed IL-15 in vivo.

N-803 is currently being evaluated for adult patients in two clinical NMIBC trials. QUILT 2.005 is investigating use of N-803 in combination with BCG for patients with BCG-naïve NMIBC; QUILT 3.032 is studying N-803 in combination with BCG in patients with BCG-unresponsive NMIBC.

Mechanism of Action & Contribution of N-803 (Anktiva) and BCG for Bladder Cancer

Trained immunity10 is a recently discovered immune system response triggered by BCG. Natural Killer (NK) and T cells11 are activated by BCG resulting in bladder cancer cell death. When an appropriate secondary stimulus is administered along with BCG, that trained immune response is enhanced to induce immune memory resulting in a prolonged duration12 of immunological response. N-803, an IL-15 superagonist which proliferates NK and T cells13, serves as this enhancing secondary boost and augments the immunological response when given in combination with BCG. This mechanism of action of inducing trained innate immune memory, through the combination of N-803 and BCG, accounts for the prolonged 24-month durable complete response reported in this trial.